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CASE REPORT Open Access
Septo-optic dysplasia with amniotic bandsyndrome sequence: a
case reportInsiyah A. Amiji1*, Ummulkheir H. Mohamed1, Adelina G.
Rutashobya1, Mariam Mngoya1, Nicole Schoenmann2,Helga E. Naburi1
and Karim P. Manji1
Abstract
Introduction: De Morsier syndrome, or septo-optic dysplasia, is
a rare, heterogeneous, complex condition with ahighly variable
phenotype. It is characterized by optic nerve hypoplasia, pituitary
gland hypoplasia, and midlinebrain abnormalities, including absence
of septum pellucidum and corpus callosum dysgenesis. Diagnosis is
madeclinically by the presence of any two or more features from the
clinical triad.
Case presentation: We report a case of a premature African
newborn male baby born to nonconsanguineousparents who presented to
our institution with agenesis of the septum pellucidum, unilateral
optic nerve hypoplasia,and pituitary stalk hypoplasia. However, he
had intact central endocrine function. He also presented with
limbdefects due to constricting amniotic band syndrome. Other
dysmorphic features were low-set ears, microcephaly,and bilateral
talipes equinovarus. He otherwise had a normal neurological
examination result. Over time, he had anadequate weight gain and
was managed by a multidisciplinary team.
Conclusion: De Morsier syndrome still represents a diagnostic
challenge, despite advances in neuroimaging andgenetic studies, due
to the heterogeneous nature of the disorder. This case adds to
existing knowledge on thevascular pathogenesis of septo-optic
dysplasia.
Keywords: Septo-optic dysplasia, Amniotic band syndrome, Optic
nerve hypoplasia, Hypopituitarism
IntroductionSepto-optic dysplasia (SOD) is a rare heterogenous
con-dition comprising optic nerve hypoplasia, midline
brainabnormalities (agenesis of corpus callosum or absence ofseptum
pellucidum), and pituitary hypoplasia with con-sequent
hypopituitarism.The majority of cases are sporadic; however,
several fa-
milial cases have been described, and the identificationof
mutations in key developmental genes, includingHESX1, SOX2, and
SOX3, suggests a genetic causation.Therefore, it is a developmental
disorder resulting froma defect of normal embryological
development. The pre-cise etiology is multifactorial, involving
contributionsfrom environmental factors and genetics [1].The
diagnosis is predominantly clinical, and it is made
on the basis of the presence of two or more features of
the classic triad: hypopituitarism, optic nerve hypoplasia,and
midline brain defects, typically absence or hypopla-sia of the
septum pellucidum and/or corpus callosum.There is evidence in the
literature of the vascular patho-
genesis of SOD [2]. However, the mechanisms of congeni-tal
constriction band syndrome with SOD are still underdebate. Theories
have been postulated that septo-optic“dysplasia” makes more sense
as a vascular disruption se-quence than as a primary developmental
anomaly.
Case presentationWe report a case of a newborn African male baby
deliv-ered at 32 weeks of gestation by cesarean section due
tobreech presentation. His birth weight was 1.9 kg
(75thpercentile), head circumference was 27 cm (< 10th
per-centile), and length was 37 cm (< 10th percentile). Hewas
the first child of nonconsanguineous parents. Hisprenatal history
was uneventful. The family had no his-tory of visual abnormalities
or neurological disorders.General examination revealed absence of
all five digits
in the right hand with a constricting band in the right
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stated.
* Correspondence: [email protected] of
Paediatric and Child Health, School of Medicine,
MuhimbiliUniversity of Health and Allied Sciences, PO Box 65001,
Dar es Salaam,TanzaniaFull list of author information is available
at the end of the article
Amiji et al. Journal of Medical Case Reports (2019) 13:370
https://doi.org/10.1186/s13256-019-2306-2
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wrist joint (Fig. 1). A similar constricting band wasfound on
the left arm (Fig. 2). Radial and brachial pulseswere palpable and
of good volume in both upper limbs,and they were synchronous with
femoral and poplitealpulses of the lower limbs. The skin of all the
limbs wasnormal in color. Other distinctive features were
thepresence low-set ears, microcephaly and bilateral
talipesequinovarus (Fig. 3). His random blood sugars werewithin
normal range, and he maintained normal body
temperature. He gained 600 g by the end of 3 weeks anddid not
experience any seizures or jitteriness throughouthis stay in the
hospital.Neurological examination revealed good muscular
tone and normal primitive reflexes, and both pupils hada normal
reaction to light. Indirect funduscopy showed anormal optic disk in
the right eye but optic nerve hypo-plasia in the left eye with
retinopathy of prematuritystage II.The patient’s serum level of
thyroid-stimulating hor-
mone was 0.59 nmol/L (normal), growth hormone levelwas 8.27
ng/ml (high), and cortisol level was 8.1 μg/dl(normal).X-ray of the
right hand showed hypoplasia of proximal
and distal phalanges (Fig. 4). Cranial ultrasound showedagenesis
of the septum pellucidum and dilation of thethird ventricle (Fig.
5).Magnetic resonance imaging of the brain revealed ab-
sence of the septum pellucidum, thin corpus callosum,hypoplastic
pituitary stalk, bilateral blunted roof of theanterior horns of the
lateral ventricles, and pachygyria.No schizencephaly was present
(Figs. 6 and 7).We could not do genetic testing, because it is
not
available in our setting.The child was managed conservatively
with a multidis-
ciplinary approach including a team of pediatricians,
Fig. 1 Left wrist after amniotic band release (arrowhead)
Fig. 2 Constricting amniotic band on right arm (arrowhead) Fig.
3 Bilateral talipes equinovarus
Amiji et al. Journal of Medical Case Reports (2019) 13:370 Page
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pediatric surgeons, and an ophthalmologist. The dur-ation of his
hospital stay was 3 weeks. During this time,he underwent
constricting amniotic band release repairof both upper limbs, and
corrective repair of the righthand was planned with plastic
surgery. Currently, thepatient is discharged, he is followed up as
an outpatientin Opthalmology clinic every month. Because he doesnot
have endocrinologic abnormalities at this stage, weplan to do a
repeat hormone profile at the age of 6months. Due to early
detection of the abnormalities andinterventions and with the
cooperation of the parents,our patient has a favorable prognosis,
which will im-prove his quality of life and survival.
DiscussionThe term “septo-optic dysplasia” was coined in 1956
byde Morsier, who pointed out the association of opticnerve
hypoplasia with an absence of the septum pelluci-dum [3]. Later, in
1970, Hoyt et al. demonstrated the as-sociation between SOD and
pituitary dwarfism [4]. SODhas been used to describe a variety of
clinical conditionsin patients with bilateral optic nerve
hypoplasia and a
Fig. 4 Hypoplasia of the right proximal and distal
phalanges(arrowhead)
Fig. 5 Thin corpus callosum (arrowhead)
Fig. 6 Absent septum pellucidum (arrowhead)
Fig. 7 Pachygyria (arrowhead)
Amiji et al. Journal of Medical Case Reports (2019) 13:370 Page
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spectrum of midline brain defects with or without
endo-crinologic abnormalities (Table 1).Diagnosis is predominantly
clinical; however, despite
advances in neuroimaging and genetic studies, it stillposes a
diagnostic challenge due to its highly variableclinical spectrum.
Our patient was diagnosed clinicallyand with evidence of
neuroimaging after birth, but mostaffected children present later
in life with failure tothrive, hypoglycemia, seizures, blindness,
and develop-mental delay.This syndrome has been linked to young
maternal age,
and it has been reported to be equivalent in males and
females. To the best of our knowledge, this is the first
casereported in an African male patient, born to nonconsan-guineous
parents. Male predominance has also been shownin Italian and Omani
children [5, 6]. Most cases reportedhave no history of
consanguinity, possibly indicating asporadic cause for this
disorder. In contrast, Ganesh et al.[6] reported the presence of
highly prevalent consanguinityin Omani children with this disorder.
Therefore, this doesnot exclude the possibility of a genetic
cause.SOD is a heterogenous, complex malformation with
high phenotypic variability; hence, all features might notbe
present in a single patient [5, 7].
Table 1 Clinical pattern of septo-optic dysplasiaFeatures Our
patient Palui et al.,
2018 [13]Ganesh et al.,2013 [6]
Signorini et al.,2012 [5]
Polizzi et al.,2006 [7]
Stevens et al.,2004 [10]
Race (children) African Indian Omani Italian Italian
American
Neurological
Midline defects
Septum pellucidum/corpus callosum
Normal – – – – – –
Absent/agenesis + + + + + –
Cerebral cortex
Normal – + + + + –
Polymicrogyria – – – + – +
Schizencephaly – – – + – –
Pachygyria + – – – – –
Other
Dysmorphic fornices – – – + + –
Ventricular abnormality + – – + – –
Cerebellar vermis hypoplasia – – – + – –
White matter abnormalities – – – – – –
Ocular
Optic nerve
Unilateral hypoplasia + – + – – –
Bilateral hypoplasia – + + + + +
Endocrine
Pituitary gland
Normal + – – – – Not reported
Absent – – – + –
Ectopic – + + – +
Pituitary stalk
Normal – + – + Not reported Not reported
Hypoplasia + – + –
Pituitary hormones
Normal + – – – + –
Low or absent – + + + + +
Additional findings
Limb defects + – – – + +
Dysmorphic features (cleft palate, cleft lip, frontal
bossing,macrocephaly, microcephaly, genital abnormalities)
+ – – – + –
Amiji et al. Journal of Medical Case Reports (2019) 13:370 Page
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Full-blown de Morsier syndrome (SOD with panhypo-pituitarism) is
seen in only in 11–30% of fully evaluatedpatients [8, 9].
Hypothalamic-pituitary dysfunction is apredominant feature in SOD.
It manifests as eitherstructural malformation in the pituitary
gland detectedby high-resolution neuroimaging or pituitary
hormoneinsufficiencies; however, only 60% show structural
ab-normalities in the brain.Our patient had midline brain defects
such as agenesis
of septum pellucidum, thinning of the corpus callosum,unilateral
optic nerve hypoplasia, and pituitary stalk hy-poplasia with intact
central endocrine function, and ourpatient showed findings similar
to those in the cases re-ported by Signorini et al. [5] in Italian
children. In viewof these findings and the possibility that hormone
defi-ciencies can emerge and evolve over time, lifelong med-ical
follow-up of these aspects may be warranted.Theories on the
vascular etiology of septo-optic “dyspla-
sia” have been postulated that it is more a vascular disrup-tion
sequence than a primary developmental anomaly [2,10]. The anatomic
correlation of the anterior cerebral ar-tery and its branches to
the optic nerves and chiasm, theanterior hypothalamus, the septum
pellucidum, and otherstructures makes it more vulnerable to
vascular events.The limb defects in our patient as well as those
previ-
ously reported are suggestive of amniotic band
disruptionsequence [8, 10, 11]. We propose that these
vascularchanges may also explain the development of features ofSOD
seen in these patients.SOD has been reported to occur with exposure
to sev-
eral teratogens, some of which are known to have
vasculareffects, including cocaine, alcohol, and
phenylpropanol-amine [12]. However, we found no such exposure
duringthe prenatal period in our patient.On the basis of the
clinical findings and evidence in
the literature, our patient presented with features sug-gestive
of SOD with limb defects due to constricting am-niotic band
sequence, indicating a possibility of vascularpathogenesis of this
syndrome.
ConclusionDe Morsier syndrome (SOD) still represents a
diagnosticchallenge. Standard diagnostic criteria together with a
highindex of suspicion in the evaluation of patients with
midlinedefects, optic nerve hypoplasia, and/or hypopituitarism
isimportant for accurate detection. Furthermore, identifica-tion of
different phenotypic profiles within the diseasespectrum can allow
more targeted follow-up of these chil-dren to reduce
disease-related morbidity and mortality,which may prevent
life-threatening sequelae. This case addsto the existing knowledge
on the vascular etiology of SOD.
AbbreviationsSOD: Septo-optic dysplasia
AcknowledgementsWe are grateful to the parents of this child,
who have been veryunderstanding, supportive, and cooperative with
us throughout.
Authors’ contributionsUHM, AGR, and MM admitted the baby and
were attending physicians of thebaby daily in the NICU. IAA
prepared the manuscript. NS, HEN, and KPM arespecialists who
provided their expert opinion in the management of this baby,and
they also helped with bedside cranial ultrasound imaging and
correctingthe manuscript. All authors read and approved the final
manuscript.
Authors’ informationInsiyah A. Amiji (Resident Doctor)Ummulkheir
H. Mohamed (Resident Doctor)Adelina G. Rutashobya (Resident
Doctor)Mariam Mngoya (General Practitioner)Helga E. Naburi
(Pediatrician)Karim P. Manji (Neonatologist)Nicole Schoenmann
(Neonatologist)
FundingNo funds were needed for this publication.
Availability of data and materialsData sharing not
applicable.
Ethics approval and consent to participateEthical approval was
not applicable. Consent for participation was given bythe
biological father.
Consent for publicationWritten informed consent was obtained
from the patient’s legal guardian(father) for publication of this
case report and any accompanying images. Acopy of the written
consent is available for review by the Editor-in-Chief ofthis
journal.
Competing interestsThe authors declare that they have no
competing interests.
Author details1Department of Paediatric and Child Health, School
of Medicine, MuhimbiliUniversity of Health and Allied Sciences, PO
Box 65001, Dar es Salaam,Tanzania. 2Asklepios Klinik Barmbek, PO
Box 22307, Hamburg, Germany.
Received: 12 August 2019 Accepted: 28 October 2019
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AbstractIntroductionCase presentationConclusion
IntroductionCase
presentationDiscussionConclusionAbbreviationsAcknowledgementsAuthors’
contributionsAuthors’ informationFundingAvailability of data and
materialsEthics approval and consent to participateConsent for
publicationCompeting interestsAuthor detailsReferencesPublisher’s
Note